Venous thromboembolism prophylaxis of a patient with MYH-9 related disease and COVID-19 infection:A case report

BACKGROUND The May-Hegglin anomaly is among a group of genetic disorders known as MYH9-related disease.Patients with inherited platelet disorders such as May-Hegglin anomaly are at a variably increased risk for bleeding due to a combination of platelet dysfunction and thrombocytopenia.Patients admitted to the hospital with coronavirus disease 2019(COVID-19)infection are at an increased risk for a venous thromboembolism event(VTE).The National Institutes of Health COVID-19 treatment guidelines recommend using a prophylactic dose of heparin as VTE prophylaxis for adults who are receiving high-flow oxygen.We describe a patient admitted for COVID-19 infection with pneumonia and a history of May-Hegglin anomaly.The patient presented a challenge to determine prophylactic anticoagulation as there are no clear guidelines for this patient population.CASE SUMMARY Herein,we describe the case of a 39-year-old woman admitted with acute hypoxic respiratory failure secondary to COVID-19 pneumonia.She had a history of May-Hegglin anomaly and demonstrated risk for bleeding since childhood,including a life-threatening bleeding event at the age of 9 years requiring blood and platelet transfusions.Her baseline platelet count was 40-50×109/L throughout her adult life.Her family history was also notable for May-Hegglin disorder in her mother,maternal uncle,maternal grandfather and her son.Computed tomography/pulmonary angiography revealed bilateral consolidative opacities consistent with multifocal pneumonia.Complete blood count was notable for platelet count of 54×109/L.She was admitted for inpatient respiratory support with high-flow oxygen per nasal cannula and was managed with guideline-directed therapy for COVID-19,including baricitinib and dexamethasone.The Hematology/Oncology consultation team was requested to assist with management of VTE prophylaxis in the setting of active COVID-19 infection and an inherited bleeding disorder.After review of the literature and careful consideration of risks and benefits,it was decided to treat the patient with prophylactic enoxaparin.She was closely monitored in the hospital for bleeding and worsening thrombocytopenia.She had no bleeding or signs of VTE.Her respiratory status improved,and she was discharged home after 5 d of hospitalization with supplemental oxygen by nasal cannula and dexamethasone.At the 6-month follow-up,the patient successfully discontinued her home oxygen use after only a few weeks following discharge.CONCLUSION The patient presented a challenge to determine prophylactic anticoagulation as anticoagulation guidelines exist for patients with COVID-19,but there are no clear guidelines for management of patients with COVID-19 and inherited bleeding disorders,particularly those with MYH9-related disease.She was discharged after recovery from the COVID-19 infection without bleeding or thrombosis.As there are no published guidelines for this situation,we present a pragmatic,informed approach to a patient with MYH9-related disease who had an indication for anticoagulation.

Single and Mitochondrial Gene Inheritance Disorder Prediction Using Machine Learning

One of the most difficult jobs in the post-genomic age is identifying a genetic disease from a massive amount of genetic data.Furthermore,the complicated genetic disease has a very diverse genotype,making it challenging to find genetic markers.This is a challenging process since it must be completed effectively and efficiently.This research article focuses largely on which patients are more likely to have a genetic disorder based on numerous medical parameters.Using the patient’s medical history,we used a genetic disease prediction algorithm that predicts if the patient is likely to be diagnosed with a genetic disorder.To predict and categorize the patient with a genetic disease,we utilize several deep and machine learning techniques such as Artificial neural network(ANN),K-nearest neighbors(KNN),and Support vector machine(SVM).To enhance the accuracy of predicting the genetic disease in any patient,a highly efficient approach was utilized to control how the model can be used.To predict genetic disease,deep and machine learning approaches are performed.The most productive tool model provides more precise efficiency.The simulation results demonstrate that by using the proposed model with the ANN,we achieve the highest model performance of 85.7%,84.9%,84.3%accuracy of training,testing and validation respectively.This approach will undoubtedly transform genetic disorder prediction and give a real competitive strategy to save patients’lives.

Infant with cardiomyopathy: When to suspect inborn errors of metabolism?

Inborn errors of metabolism are identified in 5%-26% of infants and children with cardiomyopathy. Although fatty acid oxidation disorders, lysosomal and glycogen storage disorders and organic acidurias are well-known to be associated with cardiomyopathies, emerging reports suggest that mitochondrial dysfunction and congenital disorders of glycosylation may also account for a proportion of cardiomyopathies. This review article clarifies when primary care physicians and cardiologists should suspect inborn errors of metabolism in a patient with cardiomyopathy, and refer the patient to a metabolic specialist for a further metabolic work up, with specific discussions of "red flags" which should prompt additional evaluation.

Normal epigenetic inheritance in mice conceived by in vitro fertilization and embryo transfer

An association between assisted reproductive technology （ART） and neurobehavioral imprinting disorders has been reported in many studies, and it seems that ART may interfere with imprint reprogramming. However, it has never been explored whether epigenetic erros or imprinting disease susceptibility induced by ART can be inherited transgenerationally. Hence, the aim of this study was to determine the effect of in vitro fertilization and embryo transfer （IVF-ET） on transgenerational inheritance in am inbred mouse model. Mice derived from IVF-ET were outcrossed to wild-type C57BL/6J to obtain their female and male line F2 and F3 generations. Their behavior, morphology, histology, and DNA methylation status at several important differentially methylated regions （DMRs） were analyzed by Morris water maze, hematoxylin and eosin （H＆E） staining, and bisulfite genomic sequencing. No significant differences in spatial learning or phenotypic abnormality were found in adults derived from IVF （F1） and female and male line F2 and F3 generations. A borderline trend of hypomethylation was found in H19 DMR CpG island 3 in the female line-derived F3 generation （0.40±0.118, P=0.086）. Methylation status in H19/Igf2 DMR island 1, Igf2 DMR, KvDMR, and Snrpn DMR displayed normal patterns. Methylation percentage did not differ significantly from that of adults conceived naturally, and the expression of the genes they regulated was not disturbed. Transgenerational integrity, such as behavior, morphology, histology, and DNA methylation status, was maintained in these generations, which indicates that exposure of female germ cells to hormonel stimulation and gamete manipulation might not affect the individuals and their descendents.